DESCRIPTION: (provided by the applicant): Insect development and behavior are orchestrated by hormone-driven signaling cascades. We have identified ecdysis-triggering hormones (ETHs) in flies (Drosophila, Musca) and moths (Manduca, Bombyx), demonstrated their functional roles in regulating in the ecdysis sequence, and established that ETH is obligatory for insect survival. The overall objective of this proposal is to provide a better understanding how gene expression and hormones regulate developmental and behavioral processes. Long-range goals are to provide basic knowledge eventually applicable to management of human disease vectors, e.g., mosquitoes. The specific objectives of this proposal are to define the ETH system in human disease vectors, elucidate regulatory roles of steroids in ETH signaling, and to understand the physiological roles of ETH in orchestration of the ecdysis sequence. The first objective (Specific Aim I) will be to establish the presence of the ecdysis-triggering hormone (ETH) in mosquitoes, provide basic knowledge of the ecdysis sequence in these animals, and determine the consequences of disrupting ETH signaling. For the second and third specific aims, we will make use of model systems to examine hormonal mechanisms regulating ETH synthesis and secretion in the lnka cell (Specific Aim II) and to define cellular and molecular targets for ETH (Specific Aim Ill). The ecdysis sequence is an excellent model for relating steroid and peptide signaling processes to physiology and behavior. The fruit fly Drosophila melanogaster provides powerful genetic tools for deletion and conditional expression of key genes involved in these processes, while the moth Manduca sexta offers advantages for endocrinological and physiological manipulations. Use of these models will allow us to pose testable hypotheses at many levels, and to mobilize genetic and cellular approaches appropriate to each objective. The simplicity of the epitracheal endocrine system, composed of glands containing only 1-3 cells, provides an excellent model for examination of endocrine function at the cellular, developmental, and molecular levels. Since -ecdysis is crucial for successful development of insects and other arthropods, understanding the regulatory mechanisms which underlie these precisely timed and synchronized processes should allow in the future for more sophisticated approaches to the management of insect borne disease.